In the prior art no fast working and efficient composition has been provided for preventing and/or treating common colds initiated by viral infections caused by the so-called cold viruses, such as rhino virus, corona virus, adenovirus, coxsackie virus, RS-virus, echovirus or other cold viruses yielding the usual well known cold syndromes in patients. Practically all humans suffer 2 to 3 times a year from infections in the upper respiratory passages, such as cold and flu. In general, in Denmark the majority of common colds occurring in September, October and November are caused by rhinovirus infection, whereas the majority of common cold occurring in January, February and March are caused by Coronavirus infections.
Furthermore, there is a great need for effective remedies in the increasing number of patients suffering from allergic syndromes, for example asthma, which may be initiated by common cold viruses, especially the rhinovirus.
Recent observations from a polymerase chain reaction (PCR)-study (Johnston, 1993) with naturally rhinovirus infected persons indicates that the actual range for rhinovirus infections involved in common cold syndrome probably is at least twofold higher, compared to findings obtained via the traditional cell culture techniques (40%). This indicates that up to 70-75% of all patients suffering from common colds have a rhinovirus infections ongoing either as a single infection or co-infection (Spector, 1995).
It has been estimated that the average pre-school child experiences 6-10 upper respiratory infections or common colds per year whereas the average adult experiences 2-4 (Sperber, 1989). The effects of the common cold can be uncommonly disruptive, forcing otherwise normal persons to miss work, school, etc. Individuals who are at increased risks, such as individuals suffering from bronchitis or asthma, may also experience a life-threatening exacerbation of their underlying conditions. The average annual expenditure for various cold treatments exceeds USD 2 billion in the United States, alone (Spector, 1995); in the EU a similar figure is expected.
Currently, there is no efficient treatment to offer common cold patients. Some offered treatments may even worsen the cold; for example, it has been demonstrated that the administration of aspirin and acetaminophen may have detrimental effects on cold treatment, neutralising antibodies and even increase nasal problems (Graham, 1990). Oral alpha-agonist may relieve congestions in many individuals and antihistamines may sometimes be helpful (Spector, 1995) but no real cure is observed Prevention or treatment with artificial soluble receptors has not been as successful as hoped (Hayden, 1988); several trials treating common cold patients with interferon have been completely negative (Monto, 1989; Sperber, 1989). Plecamil® which recently (March, 2000) was investigated in several trials and which inhibits the binding of the rhinovirus via its attachment site, termed also negatively.
All these trials, which involved treatment of the syndrome common cold were negative, despite the fact that adequate drug concentrations were present in the nose of the treated persons. These results indicate that reversal of the pathogenic events in rhinovirus colds requires more than just the inhibition of viral replication.
Unfortunately, research in development of novel strategies to treat common cold is complicated by the fact human rhinoviruses only have been reported to infect primates successfully and hence no practical animal model has been developed for rhinovirus infections (Rotbart, 2000).
The development of natural and experimentally induced rhinovirus infections in normal persons are initiated by selected events which can be considered to occur sequentially. The steps in the rhinovirus pathogenesis are believed to include viral entry into the outer nose, mucociliary transport of virus to the posterior pharynx, and initiation of infection in ciliated and non-ciliated epithelial cells of the upper airway. Viral replication peaks on average within 48 h of initiation of infection and persists for up to 3 weeks; Infection is followed by activation of several inflammatory mechanisms, which may include release or induction of interleukins, bradykinins, prostaglandins and possibly histamine, including simulation of parasympathetic reflexes (the cytokines may counteract each other at certain levels resulting in a very complex pathway). The resultant clinical illness is a rhinosinusitis, pharyngitis, and bronchitis, which on average lasts one week (Gwaltney, 1995).
Occasionally, a secondary bacterial or microbial infection may follow subsequently to the viral infection and a sustained and more serious inflammation may result.
Previously, it was believed that the major part of the virus was produced in the upper nose region and excreted (Winther, 1993a). However, subsequent studies, comparing recovery of virus in nasopharyngeal wash specimens, nasal swabs and pharyngeal swabs showed that the nasopharyngeal wash specimens was consistently superior to the other two specimens in yielding virus (Cate, 1964). From a series of in-depth investigations (Winther, 1984a; Winther, 1984b; Winther, 1984c; Turner, 1984; Farr, 1984; Hayden, 1987; Winther, 1987a; Winther, 1987b; Winther, 1993b; Arruda, 1995; Winther, 1998) it was concluded that:    (i) the virus was first recovered, at the highest concentrations, from the nasopharynx before it could be recovered in the upper nose region (turbinates).    (ii) no evidence for rhinovirus induced damage of the surface ciliary lining of the inferior turbinate was noted which is in agreement with other investigators suggesting that the virus may be transported to the nasopharynx in the overlaying mucus by mucociliary clearence.    (iii) there was a significant increase of the influx of neutrophils in the same area as in (ii)    (iv) infection of the lining of the nasal cavity was not uniform after intranasal inoculation and seemed not to result in any cell damage at all, cf. (ii) above.    (v) the rate of viral shedding in the nasopharynx was high by day 1 (post infection), whereas cold symptoms did not peak until day 3. The symptoms waned during the first week, but rhinovirus was present during the following 3 weeks.    (vi) The increase of neutrophils correlate with the onset of symptoms, including sore throat. The symptoms include oedema-like symptoms which, in turn, may trigger sneezing and coughing.
In summarising the above findings, it should be stressed that the highest concentration of virus can be recovered from the nasopharynx, and virus usually appears on the turbinate(s) one or two days later, despite the fact that virus is innoculated via the nose (in volunteers); no visible damage of the cell lining in the upper airways was ever demonstrated. Furthermore, as “sore throat” usually develops simultaneously with the appearance of virus in the nasopharynx it can be reasoned that “signal molecules” or the like (Van Damme, 1988) will be made by the relatively few rhinovirus cells infected and that these “cytokine-like molecules” subsequently may activate the “lymphatic ring”—which is located just beneath the nasopharynx—leading to the well-known sore throat which in turn triggers a complex pattern of inflammatory reactions, involving an array of different interferons and cytokines the interaction of which is currently under in-depth investigation. Some of these factors, such as for example II-1, induce fever in patients. Bradykinines per se may be responsible for the sore throat which is frequently associated with common cold.
The fact that interferon is known to be part of the non-specific innate immune response against viral infections in man has lead to several publications as a number of groups have investigated how much interferon is produced locally during viral infections of the upper-airways. One of the earliest and probably most thorough, in vivo, investigations in man was performed by Cate et al. (Cate, 1969) on volunteers (healthy adult males from federal correctional institutions in USA): the authors were able to demonstrate that most of the persons involved, produced interferon (as demonstrated in nasal washings) during common colds at a level which, at least theoretically, should have been enough to block the viral infection, per se. It is tempting to speculate that if no interactions from the numerous inflammatory actions (including oedemas) had taken place, the infected persons might not had experienced a traditional cold at all.
It has been demonstrated in a recent publication, that the immune system also takes “active part” in the spread of the inflammatory actions since experimental evidence supports the notion that rhinovirus may use some of the effector cells from the immune system as a mean for spreading the inflammatory reactions to the lower airways (Gem, 1996) via initiation of local TNF-alpha production; it is tempting to speculate that the allergic rhinitis is initiated via this mechanism as it has been found that the pathogenesis for asthma is linked to local TNF-alpha production (Broide et al. 1992). Several quarters have thus argued that the asthma syndromes are rhinovirus manifestations of post-infectious events triggered by an array of different cytokines in connection with a “switch” between the Th1 vs. Th2 response (Gem, 1999; Winther, 1998; Grünberg, 1999).
Generally speaking, air-way infections or allergic rhinitis and/or asthma may pose a serious health problems as it can be potentially life-threatening for susceptible groups such as elderly people with chronic airway problems or persons suffering from a deficient immunity, such as AIDS-patients, cancer patients etc. Thus, a simple method of treating these symptoms/syndromes (and possibly also the underlying infections would be of immense importance).
Viral and/or other microbial infections are known to initiate a complex inflammatory response (Ginsburg, 1988) from the patient which probably is mediated by several groups of responder cells including the neutrophile granulocytes, which are specifically increased during a cold. The latter represents approximately more than 95% of all the effector cells; each min. about 6-9 millions neutrophiles enter the upper-airways and slowly pass down the interior surfaces encompassing the upper airways; it may be assumed that the neutrophiles, which are able to release very aggressive enzymes and toxic substances upon proper stimulation will keep the bacterial load of the upper-airways to an acceptable level; the small numbers of S. pyogenes or S. aureus found in nasopharynx, which otherwise is almost sterile, may stimulate the neutrophiles via the so-called super-antigens to a certain degree thereby limiting the numbers of bacteria in said areas (dynamic equilibrium/symbiosis).
According to Ihrcke and co-workers (Ihrcke, 1993) the very early steps in a virus infection (or any other abnormality in the cell lining) can be related to the content and metabolism of heparan sulfate proteoglycan (the major proteoglycan associated with intact endothelial cells). The first element of the model derives from the observation that heparan sulfate is released from the intact endothelial lining of blood vessels during the very first step in an inflammatory response initiated by a viral infection. Accordingly, this loss may seriously compromise the vascular integrity and result in a local edema attracting further neutrophiles via the up-regulation of ICAM-1 markers on the endothelial cells increasing the inflammatory response further. Thus, in a separate experiment, activated neutrophiles were able to release 70% of all cell-associated heparan sulfate proteoglycan within one hour via the subsequent release of heparanase. One important function of heparan sulfate is the maintenance of the endothelial cell integrity. Loss of heparan sulfate partially abrogate the barrier properties of the endothelium and contributes to the edema and exudation of plasma proteins that characterise inflammation.